The reticulum cell sarcomas (RCS) of SJL mice lack macrophage and T cells but possess some B-cell surface antigens. Their surface IA molecules are slightly different from normal IAs and cause strong proliferation of syngeneic Lyt 1+, 2- T cells and of T cells only from F1 hybrids of SJL with strains lacking IE expression. No evidence for expression of foreign H-2 components on RCS cells has been obtained, and the responses are inhibited by monoclonal anti-IAs. Growth of RCS appears to depend on the ability of the host T cells to respond with proliferation and lymphokine production, including high IL-2 and gamma-IFN titers. The RCS cells play an active role in this lymphokine production, since pactamycin-\or ultraviolet-treated cells do not induce T-cell responses except when IL-2, but not when IL-1, is added to the cultures. T cells from nonresponder F1 hybrids still fail to respond even when IL-2 is added. RCS cells produce immunoregulatory effects in vivo depending on the time of injection with respect to antigen and on the nature of the antigen used.